(2-溴-5-氟苯基)氨基甲酸叔丁酯

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Place (2-bromo-5-fluoro-phenyl)-carbamic acid tert-butyl ester (2.00 g, 6.90 mmol) and dimethylformamide (40 mL) in a round bottom flask. Cool the solution to 0° C., add sodium hydride (60% dispersion in mineral oil) (0.303 g, 7.59 mmol), remove the ice bath and stir this suspension for 25 minutes allowing it to warm slowly towards ambient temperature. Cool the resulting mixture to 0° C. once again, and add iodomethane (0.56 mL, 8.96 mmol). Stir the resulting mixture overnight, allowing it to warm to ambient temperature. Quench the reaction with brine and extract the resulting mixture into ethyl acetate. Combine the extracts and wash with brine; then dry (sodium sulfate) and concentrate in vacuo. Purify the resulting material by flash chromatography (silica gel; 35%-50% dichloromethane gradient in hexanes) to provide the desired product. remove the ice bath to warm slowly towards ambient temperature Cool the resulting mixture to 0° C. once again Stir the resulting mixture overnight to warm to ambient temperature Quench the reaction with brine extract the resulting mixture into ethyl acetate wash with brine then dry (sodium sulfate) concentrate in vacuo Purify the resulting material by flash chromatography (silica gel; 35%-50% dichloromethane gradient in hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Add (2-bromo-5-fluoro-phenyl)-carbamic acid tert-butyl ester (1.06 g, 3.67 mmol), bis(pinacolato)diboron (1.03 g, 4.04 mmol), palladium(II) acetate (0.062 g, 0.28 mmol), tricyclohexylphosphine (0.103 g, 0.37 mmol) and acetonitrile (40 mL) to a round bottom flask. Stir at ambient temperature for approximately 5 minutes to dissolve most of the reagents. Add cesium fluoride (2.10 g, 13.82 mmol), place the flask in a 90° C. oil bath, and stir for 30-45 minutes. Remove the oil bath and allow the reaction mixture to cool to ambient temperature. To this mixture, add trifluoromethanesulfonic acid 6-benzyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (0.75 g, 1.22 mmol), palladium(II) acetate (0.062 g, 0.28 mmol), tricyclohexylphosphine (0.103 g, 0.37 mmol) and place the reaction in a 90° C. oil bath. Stir the reaction for 4 hours at 90° C. Cool the reaction to ambient temperature, filter it through a pad of Celite and rinse the pad with ample, hot ethyl acetate. Wash the filtrate with 50% aqueous sodium carbonate, saturated aqueous ammonium chloride, H2O and brine; then dry (sodium sulfate) and evaporate it in vacuo. Load the resulting material onto an SCX column. Wash with dichloromethane, 50% dichloro-methane/methanol, elute with ammonia solution (2N NH3 in methanol) and remove solvent under vacuum. Purify the resulting residue by flash chromatography (silica gel; 1%-5% methanol gradient in dichloromethane: followed by a second chromatography 2% of 2N NH3 in methanol/25% THF/hexanes: followed by purification on a Chromatotron; 2% MeOH/dichloromethane) to provide 0.300 g (36%) of the title compound: mass spectrum (ion spray) m/z=675 (M+H). to dissolve most of the reagents Remove the oil bath to cool to ambient temperature the reaction in a 90° C. oil bath Stir the reaction for 4 hours at 90° C Cool the reaction to ambient temperature filter it through a pad of Celite rinse the pad with ample, hot ethyl acetate Wash the filtrate with 50% aqueous sodium carbonate, saturated aqueous ammonium chloride, H2O and brine then dry (sodium sulfate) evaporate it in vacuo Wash with dichloromethane, 50% dichloro-methane/methanol elute with ammonia solution (2N NH3 in methanol) remove solvent under vacuum Purify the resulting residue by flash chromatography (silica gel followed by purification on a Chromatotron